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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/F758    most recent 90291.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Haque, M. Z. Articles by Majid, D. S. A. Search for Related Content PubMed PubMed Citation Articles by Haque, M. Z. Articles by Majid, D. S. A.

Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91^phox subunit of NAD(P)H oxidase

Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana

Submitted 13 May 2008 ; accepted in final form 29 June 2008

Both short-term and long-term nitric oxide (NO) blockade were shown to cause an increase in O₂^– activity. To assess the contribution of such enhanced O₂^– activity in the kidney, responses to administration of the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 200 µg·min^–1·kg body wt^–1) were assessed in knockout mice the lacking NAD(P)H oxidase subunit gp91^phox (KO; n = 10) and in wild-type (WT; n = 10) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances, respectively. Baseline RBF was higher in KO compared with WT mice (5.8 ± 0.5 vs. 4.5 ± 0.3 ml·min^–1·g^–1; P < 0.04) without significant differences in GFR (0.62 ± 0.04 vs. 0.73 ± 0.05 ml·min^–1·g^–1) and in mean arterial pressure (MAP; 91 ± 6 vs. 88 ± 4 mmHg). L-NAME infusion for 60 min caused similar increases in MAP (114 ± 6 vs. 113 ± 3 mmHg) in both groups but resulted in a lesser degree of reduction in RBF in KO compared with WT mice (–7 ± 3 vs. –17 ± 3%; P < 0.02), although GFR remained unchanged in both groups. The natriuretic response to systemic L-NAME infusion was attenuated in KO compared with WT mice (: 3.1 ± 0.7 vs. 5.2 ± 0.6 µmol·min^–1·g^–1). L-NAME increased urinary 8-isoprostane excretion rate in WT (5.9 ± 1 to 7.7 ± 1 pg·min^–1·g^–1; P < 0.02) but not in KO mice (5.6 ± 1 to 4.9 ± 0.3 pg·min^–1·g^–1). In contrast, responses to another vasoconstrictor, norepinephrine, were similar in both strains of mice. These data indicate that activation of NAD(P)H oxidase results in the enhancement of O₂^– activity that influences renal hemodynamics and excretory function in the condition of NO deficiency.

superoxide; oxidative stress; renal blood flow; sodium excretion; 8-isoprostane excretion